Epigenetic and mitochondrial mechanisms in aging and longevity: A report of a meeting of the Longevity Consortium, Napa, California, October 25-27, 2006

Abstract

Although the findings were diverse in technique and model systems, it appears that much of the research presented supports the central role of DNA maintenance, modification, and variation in longevity and aging. Thus, for example, Tom Prolla's research emphasized the role of mtDNA mutation in premature aging and apoptosis in a mouse model, whereas Janine Santos's observations linked the intramitochondrial localization of the DNA repair enzyme, hTERT, to stress-related mtDNA damage and cell apoptosis. There was also David Rand's presentation on the dynamic relationship between nuclear and mtDNA in establishing the contribution of mitochondria to longevity under different physiological and dietary conditions. Other examples of the centrality of DNA to much of the meeting's scientific content included work done by Judy Campisi on the Werner's gene (a recQ-like DNA helicase involved in segmental progeria) and the findings of Ben Van Houten on the role of DNA nucleotide excision repair in contributing to life-span determination in C. elegans. The involvement of still other, in these instances, nonenzymatic proteins in relationship to DNA function and aging was also illustrated in Heidi Tissenbaum's presentation on transcription factor binding to DNA and Colin Stewart's observations on the multiple roles potentially played by nuclear matrix proteins in nuclear structure and function, including the possibility that such proteins serve as a link between exogenous mechanical force, DNA, and gene expression. The latter represents a relatively underappreciated example of the great importance the environment plays in regulating DNA function and gene expression. A much more fully investigated and discussed aspect of gene (i.e., DNA)-environment interaction as it affects aging and longevity is, of course, the impact of diet (CR) on the latter processes. Eric Ravussin's presentation on CR in humans focused on this issue, albeit indirectly with regard to molecular mechanisms, but it was Jean-Pierre Issa's references to the role of environment, notably diet, in modulating DNA methylation (and, in turn, gene expression) that concretely illustrated the linkage between intracellular change and the environment. Copyright 2007 by The Gerontological Society of America.